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A curious and noticeable structural feature in Schiff bases from 2-aminoaldoses is the fact that imino tautomers arranged equatorially in the most stable ring conformation exhibit a counterintuitive reverse anomeric effect (RAE) in the mutarotational equilibrium, i.e., the most stable and abundant anomer is the equatorial one (ß). As shown by our very recent research, this effect arises from the total or partial inhibition of the exo-anomeric effect due to the presence of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen in the axial anomer (α). When the Schiff base adopts either an enamine structure or the imino group is protonated, the exo-anomeric effect is restored, and the axial α-anomer becomes the most stable species. Although the intramolecular H-bonding should appropriately be interpreted as a genuine stereoelectronic effect, the magnitude of the RAE could be affected by other structural parameters. Herein and through a comprehensive analysis of benzylidene, cinnamylidene, naphthalene, phenanthrene, and anthracene aldehydes, we show the robustness of the RAE effect, which is similar in extent to simple aldehydes screened so far, irrespective of the size and/or hydrophobicity of the substituent at the nitrogen atom.

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INTRODUCTION: Stress urinary incontinence (SUI) is a highly prevalent condition that affects between 20 and 50% of the female population. Pelvic organ prolapse (POP) can coexist with SUI and both can be addressed through a vaginal approach. However, it is unclear whether simultaneous surgery for these two conditions can influence the outcome of incontinence treatment. OBJECTIVE: To evaluate the objective and subjective effectiveness of the transobturator suburethral (TO) band by comparing two groups: group A, of patients undergoing surgery for stress urinary incontinence (SUI) by insertion of TO mesh, and group B, formed for patients requiring simultaneous correction of pelvic organ prolapse (POP) in addition to TO mesh insertion. MATERIALS AND METHODS: This is an observational, descriptive and retrospective study in which 91 patients participated: 33 (group A) underwent surgery for SUI and 58 (group B) underwent corrective surgery for pelvic organ prolapse (POP) and TO band simultaneously. Variables included: total urinary continence, objective urinary continence, subjective urinary continence (satisfaction levels and two validated questionnaires (PGI-1 and ICIQ-SF)) and complications. RESULTS: Regarding total continence, from the seventh to the ninth year, statistically significant differences were observed, with total continence being higher in group A. Objective continence decreased in both groups during the follow-up period. No significant differences were found between the two groups regarding subjective urinary continence (ICIQ-SF) and the degree of improvement after surgical treatment (PGI-1). The level of satisfaction after surgery was high in both groups. Regarding complications, there were no statistically significant differences. CONCLUSIONS: Isolated surgery for SUI could be considered more effective in achieving total and objective continence. However, the insertion of the TO band in both cases improves subjective urinary continence and quality of life with great safety and without differences regarding complications.

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Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

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Background: Obstructive sleep apnea (OSA) is a highly prevalent sleep-disordered breathing. It is associated with adverse co-morbidities, being the most scientific evidence of cardiovascular (CV) disease. Currently, OSA is measured through the apnea-hypopnea index (AHI), the total number of respiratory events per hour of sleep. However, different studies have questioned its utility in OSA management, highlighting the need to search for new parameters that better reflect the heterogeneity of the disease. Hypoxic burden (HB) has emerged as a novel biomarker that informs about the frequency, duration and depth of the desaturation related to the respiratory events. We conducted a systematic review in order to find publications about the heterogeneity of OSA measured by HB and its associations with future disease. Methods: Systematic review was conducted using PubMed and Web of Science. The terms "sleep apne" and "hypoxic burden" were used to look for publications from the date of inception to August 15, 2023. Inclusion criteria: articles in English published in peer-reviewed journals. Exclusion criteria: (1) not available publications; (2) duplicated articles; (3) letters, editorials, and congress communications; (4) articles not including information about HB as a specific biomarker of OSA. Results: 33 studies were included. The results were classified in 2 main sections: (1) HB implication in the CV sphere: HB showed to be a better predictor of CV risk in OSA patients than traditional measures such as AHI with possible clinical management implication in OSA. (2) HB response to OSA treatment: pharmacological and nonpharmacological treatments have demonstrated to be effective in improving hypoxia measured through the HB. Conclusions: HB could be a better and more effective parameter than traditional measurements in terms of diagnosis, risk prediction and therapeutic decisions in patients with OSA. This measure could be incorporated in sleep units and could play a role in OSA management, driving the clinic to a more personalized medicine.

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INTRODUCTION: The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed. METHODS: Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment. RESULTS: After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (ß coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (ß coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis. CONCLUSION: Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.

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Duchenne muscular dystrophy (DMD) is characterised by respiratory muscle injury, inflammation, fibrosis and weakness, ultimately culminating in respiratory failure. The dystrophin-deficient mouse model of DMD (mdx) shows evidence of respiratory muscle remodelling and dysfunction contributing to impaired respiratory system performance. The antioxidant N-acetylcysteine (NAC) has been shown to exert anti-inflammatory and anti-fibrotic effects leading to improved respiratory muscle performance in a range of animal models of muscle dysfunction, including mdx mice, following short-term administration (2 weeks). We sought to build on previous work by exploring the effects of chronic NAC administration (3 months) on respiratory system performance in mdx mice. One-month-old male mdx mice were randomised to receive normal drinking water (n = 30) or 1% NAC in the drinking water (n = 30) for 3 months. At 4 months of age, we assessed breathing in conscious mice by plethysmography followed by ex vivo assessment of diaphragm force-generating capacity. Additionally, diaphragm histology was performed. In separate studies, in anaesthetised mice, respiratory electromyogram (EMG) activity and inspiratory pressure across a range of behaviours were determined, including assessment of peak inspiratory pressure-generating capacity. NAC treatment did not affect force-generating capacity of the mdx diaphragm. Collagen content and immune cell infiltration were unchanged in mdx + NAC compared with mdx diaphragms. Additionally, there was no significant effect of NAC on breathing, ventilatory responsiveness, inspiratory EMG activity or inspiratory pressure across the range of behaviours from basal conditions to peak system performance. We conclude that chronic NAC treatment has no apparent beneficial effects on respiratory system performance in the mdx mouse model of DMD suggesting limited potential of NAC treatment alone for human DMD.

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The reverse anomeric effect is usually associated with the equatorial preference of nitrogen substituents at the anomeric center. Once postulated as another anomeric effect with explanations ranging from electrostatic interactions to delocalization effects, it is now firmly considered to be essentially steric in nature. Through an extensive research on aryl imines from 2-amino-2-deoxyaldoses, spanning nearly two decades, we realized that such substances often show an anomalous anomeric behavior that cannot easily be rationalized on the basis of purely steric grounds. The apparent preference, or stabilization, of the ß-anomer takes place to an extent that not only neutralizes but also overcomes the normal anomeric effect. Calculations indicate that there is no stereoelectronic effect opposing the anomeric effect, resulting from the repulsion between electron lone pairs on the imine nitrogen and the endocyclic oxygen. Such data and compelling structural evidence unravel why the exoanomeric effect is largely inhibited. We are now confident, as witnessed by 2-iminoaldoses, that elimination of the exo-anomeric effect in the α-anomer is due to the formation of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen, thereby accounting for a true electronic effect. In addition, discrete solvation may help justify the observed preference for the ß-anomer.

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BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. FINDINGS: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group. CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease. TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.

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INTRODUCTION: People with chronic hepatitis C virus (HCV; PWHC) use cigarettes at a much higher prevalence than other individuals, and smoking can exacerbate the harms specifically related to HCV (eg, hepatocellular carcinoma). Little is known about factors related to cigarette use among PWHC. AIMS AND METHODS: This study examined focus group data to explore beliefs and behaviors related to cigarette use among PWHC. Qualitative data from two focus groups of PWHC reporting current cigarette smoking (n = 15, 60% male) were collected using a semi-structured interview guide. Participants were asked about reasons for smoking, barriers to quitting smoking, and the relationship of HCV to smoking. Focus groups were transcribed verbatim and coded in NVivo 12. Four coders examined themes that arose in the focus groups. Common themes are described and supported with quotes. RESULTS: Reasons for smoking included addiction to cigarettes, stress, substituting cigarettes for other drugs, and social norms, while reasons for quitting included health and being free from the use of all drugs. Barriers to quitting included concerns about coping with stress, weight gain, and having a lack of support for and education about quitting. Many participants believed there was a link between smoking and HCV and discussed smoking in relation to the stress of an HCV diagnosis. CONCLUSIONS: Participants identified both HCV-related and non-HCV-related aspects of cigarette smoking and cessation-related behaviors that could be targeted in cessation treatment. More research is needed to identify the best treatment approaches that reduce the significant medical consequences of cigarette use among PWHC. IMPLICATIONS: People with chronic hepatitis C virus (HCV; PWHC) smoke cigarettes at a high prevalence, yet little is known about their smoking behaviors. Moreover, there are no cessation treatments targeting PWHC. This is the first study to collect focus group data from PWHC who smoke in order to identify reasons for cigarette use (HCV-related and non-HCV-related), and motivators and barriers to quitting cigarettes. PWHC reports using cigarettes to cope with the stress of an HCV diagnosis and to celebrate HCV cure. These findings suggest there are specific times during the HCV care continuum where providers can aid with cessation efforts.

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Exposure to risk factors in youth can exacerbate the development of future cardiovascular disease (CVD). Obstructive sleep apnea (OSA), characterized by repetitive episodes of airway obstructions, could trigger said CVD acting as a modifiable risk factor. Measurements from echocardiography have shown impairments in the anatomy and function of the heart related to the severity of OSA. Therefore, the aim of this review was to propose a new clinical approach to the management of cardiovascular risk (CVR) in children based on treating OSA. The review includes studies assessing echocardiographic parameters for cardiac function and structure in pediatric OSA diagnosed using the apnea-hypopnea index (AHI) ≥ 1/h using polysomnography (PSG) and conducted within a year. Based on the reviewed evidence, in addition to PSG, echocardiography should be considered in OSA children in order to indicate the need for treatment and to reduce their future CVR. A follow-up echocardiography after treatment could be performed if impairments in the anatomy and function were found. Prioritizing parameters intimately connected to comorbidity could propel more effective patient-centered care. In conclusion, a reevaluation of pediatric OSA strategies should be considered, emphasizing comorbidity-related parameters in the cardiovascular field. Further studies are needed to assess this approach, potentially leading to enhanced protocols for more effective pediatric OSA treatment and CVR prevention.

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Cervical vertebrae may exhibit the anomalous presence of a double transverse foramen (DTF) that may impact the anatomy of related structures that traverse the cervical region, such as the vertebral artery (VA). This retrospective anatomical study utilized CT angiography cervical scans to examine the prevalence of DTF, VA, and TF areas. The subjects were separated into two groups: normal TF (NTF group; 26 males and 21 females) and double TF (DTF group; 21 males and 24 females). The males presented significantly higher TF area values (30.31 ± 4.52 mm2) than the females (27.48 ± 1.69 mm2) in the NTF group (p = 0.006). The sex differences disappeared when a DTF was present (p = 0.662). There were no differences in the VA area values between the sexes in both the NTF and DTF groups (p = 0.184). No significant differences in the VA area values between males of the NTF and DTF groups (p = 0.485) were noted. The DTF subjects presented an increased VA/TF area ratio than the NTF subjects (p < 0.001). This study showed that DTF presence reduced the TF area. In contrast, the VA area did not change despite the decreasing TF area. This might be an anatomical risk for transient vertebrobasilar insufficiency in subjects with DTF, especially in females, because VA space in the TF is less in DTF subjects than in NTF subjects. This may lead to easy VA compression in DTF subjects following neck trauma.

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While the association of obstructive sleep apnea (OSA) with an increased cardiovascular risk (CVR) in the adult population is well known, there is insufficient evidence to affirm something similar in the pediatric population. On the other hand, adenotonsillectomy has been shown to be an effective treatment. Our objective was to evaluate the association of sleep respiratory disorders in children with increased CVR and the impact of adenotonsillectomy in the literature. To this aim, a literature search was conducted, between 2002 to the present. After carrying out a systematic review, the following results were provided: thoracic echocardiography after surgery found improvements in terms of cardiac function and structure; blood pressure (BP) measurement, verified a tendency to higher BP values in the OSA pediatric population, which improved after surgery; different biomarkers of CVR, were increased in OSA patients and improved after treatment and finally; some studies found endothelial dysfunction in pediatric OSA, a measurement of vascular system function, was reversible with adenotonsillectomy. Increases in BP parameters, biological markers related to CVR and alterations in cardiac function structure, have been reported in pediatric patients with OSA. At least, some of these parameters would be reversible after adenotonsillectomy, reflecting a possible reduction in CVR.

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The development of diagnostic methods to accurately assess the effects of treatments on lithobiont colonization remains a challenge for the conservation of Cultural Heritage monuments. In this study, we tested the efficacy of biocide-based treatments on microbial colonization of a dolostone quarry, in the short and long-term, using a dual analytical strategy. We applied a metabarcoding approach to characterize fungal and bacterial communities over time, integrated with microscopy techniques to analyze the interactions of microorganisms with the substrate and evaluate the effectiveness. These communities were dominated by the bacterial phyla Actinobacteriota, Proteobacteria and Cyanobacteria, and the fungal order Verrucariales, which include taxa previously reported as biodeteriogenic agents and observed here associated with biodeterioration processes. Following the treatments, changes over time in the abundance profiles depend on taxa. While Cyanobacteriales, Cytophagales and Verrucariales decreased in abundance, other groups, such as Solirubrobacteriales, Thermomicrobiales and Pleosporales increased. These patterns could be related not only to the specific effects of the biocide on the different taxa, but also to different recolonization abilities of those organisms. The different susceptibility to treatments could be associated with the inherent cellular properties of different taxa, but differences in biocide penetration to endolithic microhabitats could be involved. Our results demonstrate the importance of both removing epilithic colonization and applying biocides to act against endolithic forms. Recolonization processes could also explain some of the taxon-dependent responses, especially in the long-term. Taxa showing resistance, and those benefiting from nutrient accumulation in the form of cellular debris following treatments, may have an advantage in colonizing treated areas, pointing to the need for long-term monitoring of a wide range of taxa. This study highlights the potential utility of combining metabarcoding and microscopy to analyze the effects of treatments and design appropriate strategies to combat biodeterioration and establish preventive conservation protocols.

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Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often underdiagnosed.We have developed a murine model of gestational OSA to study IH effects on pregnant mothers, placentas, fetuses, and offspring. One group of pregnant rats was exposed to IH during the last 2 weeks of gestation (GIH). One day before the delivery date, a cesarean section was performed. Other group of pregnant rats was allowed to give birth at term to study offspring's evolution.Preliminary results showed no significant weight differences in mothers and fetuses. However, the weight of GIH male offspring was significantly lower than the controls at 14 days (p < 0.01). The morphological study of the placentas showed an increase in fetal capillary branching, expansion of maternal blood spaces, and number of cells of the external trophectoderm in the tissues from GIH-exposed mothers. Additionally, the placentas from the experimental males were enlarged (p < 0.05). Further studies are needed to follow the long-term evolution of these changes to relate the histological findings of the placentas with functional development of the offspring in adulthood.

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This work analyzes the impact of two conditions, intermittent hypoxia exposure and high-fat diet in rats as models of sleep apnea. We studied the autonomic activity and histological structure of the rat jejunum and whether the overlapping of both conditions, as often observed in patients, induces more deleterious effects on the intestinal barrier. We found alterations in jejunum wall histology, predominantly in HF rats, based on increased crypt depth and submucosal thickness, as well as decreased muscularis propria thickness. These alterations were maintained with the IH and HF overlap. An increase in the number and size of goblet cells in the villi and crypts and the infiltration of eosinophils and lymphocytes in the lamina propria suggest an inflammatory status, confirmed by the increase in plasma CRP levels in all experimental groups. Regarding the CAs analysis, IH, alone or combined with HF, causes a preferential accumulation of NE in the catecholaminergic nerve fibers of the jejunum. In contrast, serotonin increases in all three experimental conditions, with the highest level in the HF group. It remains to be elucidated whether the alterations found in the present work could affect the permeability of the intestinal barrier, promoting sleep apnea-induced morbidities.

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Obstructive sleep apnea (OSA) in children is a prevalent, but still, today, underdiagnosed illness, which consists of repetitive episodes of upper airway obstruction during sleep with important repercussions for sleep quality. OSA has relevant consequences in the pediatric population, mainly in the metabolic, cardiovascular (CV), and neurological spheres. However, contrary to adults, advances in diagnostic and therapeutic management have been scarce in the last few years despite the increasing scientific evidence of the deleterious consequences of pediatric OSA. The problem of underdiagnosis and the lack of response to treatment in some groups make an update to the management of OSA in children necessary. Probably, the heterogeneity of OSA is not well represented by the classical clinical presentation and severity parameters (apnea/hypopnea index (AHI)), and new strategies are required. A specific and consensus definition should be established. Additionally, the role of simplified methods in the diagnosis algorithm should be considered. Finally, the search for new biomarkers for risk stratification is needed in this population. In conclusion, new paradigms based on personalized medicine should be implemented in this population.

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Kikuchi-Fujimoto disease (KFD) is an autoimmune condition that is more common in females and occurs in the third decade of life. The condition is usually benign and self-resolving and is characterized by fever, cervical lymphadenopathy, night sweats, myalgia, and rashes. The disease can be misdiagnosed as reactive follicular hyperplasia, tuberculous lymphadenitis, systemic lupus erythematosus, and malignant lymphoma. The diagnosis of KFD involves the excision of the affected lymph node. Although there is no specific treatment for the disease, usually symptomatic and supportive measures are effective; however, steroids and immunosuppressive therapies are considered in more severe cases. The disease lasts for around one to four months. The neurological complications include cerebellar ataxia, meningoencephalitis, and aseptic meningitis. Here, we describe the case of a 36-year-old male who presented with complaints of fever, malaise chills, anorexia, and fatigue associated with a tender right axillary lymph node. The patient underwent a biopsy which confirmed KFD and responded well to supportive therapy.

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Obstructive sleep apnea (OSA) has been identified as a cardiovascular (CV) risk factor. The potential of OSA promoting the synthesis of CV biomarkers in acute coronary syndrome (ACS) is unknown. Ischemia-modified albumin (IMA) has been identified as a specific CV biomarker. The aim of this study was to evaluate the role of IMA as a potential biomarker for determining the impact of OSA in ACS patients. A total of 925 patients (15.5% women, age: 59 years, body mass index: 28.8 kg/m2) from the ISAACC study (NCT01335087) were included. During hospitalization for ACS, a sleep study for OSA diagnosis was performed and blood samples extraction for IMA determination were obtained. IMA values were significantly higher in severe OSA (median (IQR), 33.7 (17.2-60.3) U/L) and moderate (32.8 (16.9-58.8) U/L) than in mild/no OSA (27.7 (11.8-48.6) U/L) (p = 0.002). IMA levels were very weakly related to apnea-hypopnea index (AHI) as well as hospital and intensive care unit stay, although they only maintained a significant relationship with days of hospital stay after adjusting for sex, age and BMI (ß = 0.410, p = 0.013). The results of the present study would suggest a potentially weaker role of OSA in the synthesis of the CV risk biomarker IMA in patients with ACS than in primary prevention.

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